ArticleInvestigative ophthalmology & visual science2011
Free insulin-like growth factor binding protein-3 (IGFBP-3) reduces retinal vascular permeability in association with a reduction of acid sphingomyelinase (ASMase).
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- Comparative Tear Fluid Proteomics to Explore Treatment Responsiveness in Diabetic Macular Edema: A Pilot Study.Journal of proteome research · 2025Article
- Tetraspanin-enriched membrane domains regulate vascular leakage by altering membrane cholesterol accessibility to balance antagonistic GTPases.Nature cardiovascular research · 2025Article
- Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy.Cell metabolism · 2024Article
- Signaling Pathways of the Insulin-like Growth Factor Binding Proteins.Endocrine reviews · 2023Article
- Role of Insulin-Like Growth Factor Binding Protein-3 in the Pathogenesis of Herpes Stromal Keratitis.Investigative ophthalmology & visual science · 2020Article
- Insulin-like Growth Factor and its Therapeutic Potential for Diabetes Complications - Mechanisms and Metabolic Links: A Review.The review of diabetic studies : RDS · 2020Review
- Review: Role of cAMP signaling in diabetic retinopathy.Molecular vision · 2020Review
- Models of retinal diseases and their applicability in drug discovery.Expert opinion on drug discovery · 2018Review
- Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy.EBioMedicine · 2016Article
- Role of Acid Sphingomyelinase in Shifting the Balance Between Proinflammatory and Reparative Bone Marrow Cells in Diabetic Retinopathy.Stem cells (Dayton, Ohio) · 2016Article
- Involvement of p53 in insulin-like growth factor binding protein-3 regulation in the breast cancer cell response to DNA damage.Oncotarget · 2015Article
- Beta-adrenergic receptor agonist decreases VEGF levels through altered eNOS and PKC signaling in diabetic retina.Growth factors (Chur, Switzerland) · 2015Article
- IGFBP-3 reduces eNOS and PKCzeta phosphorylation, leading to lowered VEGF levels.Molecular vision · 2015Article
- IGF binding proteins in cancer: mechanistic and clinical insights.Nature reviews. Cancer · 2014Review
- IGFBP-3 and TNF-α regulate retinal endothelial cell apoptosis.Investigative ophthalmology & visual science · 2013Article
- Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions.Journal of cell communication and signaling · 2013Article
- An ocular view of the IGF-IGFBP system.Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 2013Review
- Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow.Diabetes · 2013Article
- Article
- Role of the retinal vascular endothelial cell in ocular disease.Progress in retinal and eye research · 2013Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
purposeTo examine the effect of free insulin-like growth factor (IGF) binding protein-3 (IGFBP-3), independent of the effect of insulin-like growth factors, in modulating retinal vascular permeability.
methodsWe assessed the ability of a form of IGFBP-3 that does not bind IGF-1 (IGFBP-3NB), to regulate the blood retinal barrier (BRB) using two distinct experimental mouse models, laser-induced retinal vessel injury and vascular endothelial growth factor (VEGF)-induced retinal vascular permeability. Additionally, in vitro studies were conducted. In the animal models, BRB permeability was quantified by intravenous injection of fluorescein labeled serum albumin followed by digital confocal image analysis of retinal flat-mounts. Claudin-5 and vascular endothelial-cadherin (VE-cadherin) localization at interendothelial junctions was studied by immunofluorescence. In vitro changes in transendothelial electrical resistance (TEER) and flux of fluorescent dextran in bovine retinal endothelial monolayers (BREC) were measured after IGFBP-3NB treatment. Acid (ASMase) and neutral (NSMase) sphingomyelinase mRNA levels and activity were measured in mouse retinas.
resultsFour days postinjury, laser-injured mouse retinas injected with IGFBP-3NB plasmid demonstrated reduced vascular permeability compared with retinas of laser-injured mouse retinas injected with control plasmid. IGFBP-3NB administration resulted in a significant decrease in laser injury-associated increases in ASMase and NSMase mRNA and activity when compared with laser alone treated mice. In vivo, intravitreal injection of IGFBP-3NB reduced vascular leakage associated with intravitreal VEGF injection. IGFBP-3NB partially restored VEGF-induced in vivo permeability and dissociation of claudin-5 and VE-cadherin at junctional complexes. When IGFBP-3NB was applied basally to bovine retinal endothelial cells (BREC) in vitro, TEER increased and macromolecular flux decreased.
conclusionsIntravitreal administration of IGFBP-3NB preserves junctional integrity in the presence of VEGF or laser injury by reducing BRB permeability in part by modulating sphingomyelinase levels.
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